Probiotic Bacterium Prevents Cytokine-induced Apoptosis in Intestinal Epithelial Cells

Abstract

Probiotic bacteria are microorganisms that benefit the host by preventing or ameliorating disease. However, little information is known regarding the scientific rationale for using probiotics as alternative medicine. The purpose of this paper is to investigate the mechanisms of probiotic beneficial effects on intestinal cell homeostasis. We now report that one such probiotic, Lactobacillus rhamnosus GG (LGG), prevents cytokineinduced apoptosis in two different intestinal epithelial cell models. Culture of LGG with either mouse or human colon cells activates the anti-apoptotic Akt/protein kinase B. This model probiotic also inhibits activation of the pro-apoptotic p38/mitogen-activated protein kinase by tumor necrosis factor, interleukin-1␣, or ␥-interferon. Furthermore, products recovered from LGG culture broth supernatant show concentration-dependent activation of Akt and inhibition of cytokine-induced apoptosis. These observations suggest a novel mechanism of communication between probiotic microorganisms and epithelia that increases survival of intestinal cells normally found in an environment of pro-apoptotic cytokines.

VSL#3 probiotic treatment reduces chemotherapy-induced diarrhoea and weight loss

“…[20][21][22] Proposed mechanisms for probiotic-induced protection from apoptosis include activation of the anti-apoptotic Akt/protein kinase B and also through inhibition of the pro-apoptotic p38/mitogen activated protein kinase. 19 It was interesting to note that apoptosis was reduced only in the rats which received VSL#3 both before and following irinotecan. This may indicate that VSL#3 works in two ways to prevent cell death following chemotherapy.…”

“…This finding is supported by the work carried out by Yan and Polk. 19 They showed that probiotic treatment prevents intestinal epithelial cell apoptosis in response to tumour necrosis factor (TNF), interleukin-1 alpha (IL-1a) and g interferon (IFN). 19 These pro-inflammatory factors have been implicated in the pathogenesis of chemotherapy-induced mucositis.…”

“…19 They showed that probiotic treatment prevents intestinal epithelial cell apoptosis in response to tumour necrosis factor (TNF), interleukin-1 alpha (IL-1a) and g interferon (IFN). 19 These pro-inflammatory factors have been implicated in the pathogenesis of chemotherapy-induced mucositis. [20][21][22] Proposed mechanisms for probiotic-induced protection from apoptosis include activation of the anti-apoptotic Akt/protein kinase B and also through inhibition of the pro-apoptotic p38/mitogen activated protein kinase.…”

Innate mechanisms for Bifidobacterium lactis to activate transient pro‐inflammatory host responses in intestinal epithelial cells after the colonization of germ‐free rats

“…Indeed, ligand-specific activation of the TLR2 system greatly enhance transepithelial resistance in IEC lines associated with apical tightening and sealing of tight junction-associated ZO-1. 45 In addition, Yang and Polk suggested that L. rhamnosus GG inhibits tumour necrosis factor (TNF)-mediated pro-apoptotic mechanisms in IEC YAMC cultures through the blockade of TNF-induced p38 MAPK activation 46 . Interestingly and consistent with our data, one mechanism to trigger antiapoptotic signalling pathways includes the induction of the NF-jB signalling cascade.…”

Probiotics and health: An evidence-based review

“…In fact: (1) probiotics modulate and stabilize the composition of the microbiota and, therefore, may have immunomodulatory effects; (2) some probiotics are able to inhibit the inflammatory response of the intestinal immune system through inhibition of NF-B activation or in combination with an anti-apoptotic action on intestinal epithelial cells [31,32]; (3) some probiotics are able to increase the activity of Natural Killer (NK) cells [33,34], which are first line of defense as they can perform cytotoxic activities independent from prior sensitization to antigens; (4) some probiotics increase the secretion of mucus [22]; (5) some probiotics have a direct immunomodulatory action: after being captured in the Peyer's patches, they can induce the secretion of cytokines and the expression of co-stimulatory molecules by antigen presenting cells (APC) [35]; (6) some strains of lactobacilli induce dendritic cells (DC) maturation [36]. DC can, through their particular cytostructure, pass through the layer of epithelial cells and capture antigens directly from the lumen.…”